POS1232 LONG-TERM OUTCOMES OF COVID-19 VACCINATION IN PATIENTS WITH RARE AND COMPLEX CONNECTIVE TISSUE DISEASES: AN AD-INTERIM ANALYSIS OF ERN-ReCONNET VACCINATE STUDY
Authors: F. Di Cianni, C. Cardelli, N. Italiano, E. Laurino, M. Moretti, R. Depascale, A. Gamba, L. Iaccarino, A. Doria, M. J. Sousa Bandeira, S. P. Dinis, V. C Romão, E. Alessandri, E. Gotelli, S. Paolino, N. DI Giosaffatte, P. Grammatico, A. Ferraris, L. Cavagna, C. Montecucco, V. Longo, L. Beretta, I. Cavazzana, M. Fredi, A. Tincani, R. D’urzo, S. Bombardieri, G. R. Burmester, M. Cutolo, J. E. Fonseca, C. H. Frank, I. Galetti, E. Hachulla, F. Houssiau, D. Marinello, U. Müller-Ladner, M. Schneider, V. Smith, R. Talarico, J. M. Van Laar, A. Vieira, C. Tani, M. Mosca
Journal: Annals of the Rheumatic Diseases (2022)

Background Since the COVID-19 vaccination campaign was launched all over Europe, there has been general agreement on how benefits of SARS-CoV2 vaccines outweigh the risks in patients with rare connective tissue diseases (rCTDs). Yet, there is still limited evidence regarding safety and efficacy of such vaccines in these patients, especially in the long-term. For this reason, in the framework of ERN-ReCONNET, an observational long-term study (VACCINATE) was designed in order to explore the long-term outcome of COVID-19 vaccination in rCTDs patients. The consent form was developed thanks to the involvement of the ERN ReCONNET ePAG Advocates (European Patients Advocacy Group). Objectives To evaluate the safety profile of COVID-19 vaccination in rCTDs patients and the potential impact on disease activity. Primary endpoints were the prevalence of adverse events (AEs) and of disease exacerbations post-vaccination. Secondary endpoints were the proportion of serious adverse events (SAEs) and adverse events of special interest for COVID-19 (adapted from https://brightoncollaboration.us/wp-content/uploads/2021/01/SO2_D2.1.2_V1.2_COVID-19_AESI-update-23Dec2020-review_final.pdf ) Methods The first ad-interim analysis of the VACCINATE study involved 9 ERN-ReCONNET Network centres. Patients over 18 years of age with a known rCTD and who received vaccine against COVID-19 were eligible for recruitment. Demographic data and diagnoses were collected at the time of enrolment, while the appearance of AEs and potential disease exacerbations were monitored after one week from each vaccination dose, and then after 4, 12 and 24 weeks from the second dose. A disease exacerbation was defined as at least one of the following: new manifestations attributable to disease activity, hospitalization, increase in PGA from previous evaluation, addition of corticosteroids or immunosuppressants. Results A cohort of 300 patients (261 females, mean age 52, range 18-85) was recruited. Systemic lupus erythematosus (44%) and systemic sclerosis (16%) were the most frequent diagnoses, followed by Sjogren’s syndrome (SS,12%), idiopathic inflammatory myositis (IMM,10%), undifferentiated connective tissue disease (UCTD,8%), mixed connective tissue disease (MCTD,4%), Ehlers-Danlos’s syndrome (EDS,4%), antiphospholipid syndrome (APS,2%). AEs appearing 7 days after the first and second doses were reported in 93 (31%) and 96 (32%) patients respectively, mainly represented by fatigue, injection site reaction, headache, fever and myalgia. Otitis, urticaria, Herpes Simplex-related rash, stomatitis, migraine with aura, vertigo, tinnitus and sleepiness were reported with very low frequency. Less than 2% of patients experienced AEs within 24 weeks from the second dose. No SAEs or AEs of special interest were observed in the study period. There were 25 disease exacerbations (8%), 7 of which severe. The highest number of exacerbations was observed after 4 weeks from the second dose (12 within week 4, 6 within week 12 and 7 within week 24). Disease exacerbation was most frequent in patients with EDS (33%) and MCTD (25%). Conclusion This preliminary analysis shows that COVID-19 vaccination is safe in rCTDs patients. AEs appear most often early after vaccination and are usually mild. Disease exacerbations are not frequent, but can be potentially severe and tend to occur most frequently within the first month after vaccination. Exacerbations can also occur 3-6 months after vaccination, although a causal relationship with the vaccination remains to be established. Our present data underline the importance of long-term observational studies. Table 1. AEs and disease exacerbations per disease Diagnosis Patients enrolled (%) (n=300) EAs after 1 st and 2 nd dose (%) Exacerbations (%) APS 2 57 14 EDS 4 50 33 IIM 10 52 7 MCTD 4 42 25 SS 12 59 8 SLE 44 69 8 SSC 16 49 2 UCTD 8 50 - Acknowledgements VACCINATE is a study promoted by the European Reference Network on rare and complex connective tissue diseases, ERN ReCONNET. This publication was funded by the European Union’s Health Programme (2014-2020) Disclosure of Interests None declared